Variant chr1-22081706-A-AT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001791.4(CDC42):c.106-9dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00872 in 1,563,968 control chromosomes in the GnomAD database, including 69 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0072 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0089 ( 62 hom. )

Consequence

CDC42
NM_001791.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.88

Variant links:

Genes affected

CDC42 (HGNC:1736): (cell division cycle 42) The protein encoded by this gene is a small GTPase of the Rho-subfamily, which regulates signaling pathways that control diverse cellular functions including cell morphology, migration, endocytosis and cell cycle progression. This protein is highly similar to Saccharomyces cerevisiae Cdc 42, and is able to complement the yeast cdc42-1 mutant. The product of oncogene Dbl was reported to specifically catalyze the dissociation of GDP from this protein. This protein could regulate actin polymerization through its direct binding to Neural Wiskott-Aldrich syndrome protein (N-WASP), which subsequently activates Arp2/3 complex. Alternative splicing of this gene results in multiple transcript variants. Pseudogenes of this gene have been identified on chromosomes 3, 4, 5, 7, 8 and 20. [provided by RefSeq, Apr 2013]

CDC42 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 1-22081706-A-AT is Benign according to our data. Variant chr1-22081706-A-AT is described in ClinVar as [Benign]. Clinvar id is 1165494.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1103 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CDC42	NM_001791.4 linkuse as main transcript	c.106-9dup	splice_polypyrimidine_tract_variant, intron_variant	ENST00000656825.1
CDC42	NM_001039802.2 linkuse as main transcript	c.106-9dup	splice_polypyrimidine_tract_variant, intron_variant
CDC42	NM_044472.3 linkuse as main transcript	c.106-9dup	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC42	ENST00000656825.1 linkuse as main transcript	c.106-9dup		splice_polypyrimidine_tract_variant, intron_variant			NM_001791.4	P3	P60953-2

Frequencies

GnomAD3 genomes

AF:

0.00725

AC:

1103

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00143

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.0160

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00814

GnomAD3 exomes

AF:

0.00741

AC:

1849

AN:

249480

Hom.:

AF XY:

0.00743

AC XY:

1002

AN XY:

134866

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00414

Gnomad ASJ exome

AF:

0.00270

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00518

Gnomad FIN exome

AF:

0.0122

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.00759

GnomAD4 exome

AF:

0.00888

AC:

12534

AN:

1411768

Hom.:

Cov.:

AF XY:

0.00880

AC XY:

6205

AN XY:

705226

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00486

Gnomad4 ASJ exome

AF:

0.00283

Gnomad4 EAS exome

AF:

0.0000507

Gnomad4 SAS exome

AF:

0.00524

Gnomad4 FIN exome

AF:

0.0125

Gnomad4 NFE exome

AF:

0.00997

Gnomad4 OTH exome

AF:

0.00754

GnomAD4 genome

AF:

0.00725

AC:

1103

AN:

152200

Hom.:

Cov.:

AF XY:

0.00759

AC XY:

565

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00634

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.0160

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.00630

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

CDC42-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 26, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over